Abstract CT038: Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage SCLC: A phase 3 trial
Authors: Ying Cheng, Jie Wang, Caicun Zhou, Wenxiu Yao, Qiming Wang, Xuhong Min, Gongyan Chen, Xingxiang Xu, Xingya Li, Fei Xu, Yong Fang, Runxiang Yang, Guohua Yu, Youling Gong, Jun Zhao, Yun Fan, Quan Liu, Lejie Cao, Yu Yao, Yunpeng Liu, Xiaoling Li, Jingxun Wu, Zhiyong He, Kaihua Lu, Liyan Jiang, Huiqing Yu, Chengping Hu, Wenhua Zhao, Jian Zhao, Gang Wu, Dingzhi Huang, Chengshui Chen, Cuimin Ding, Baihong Zhang, Xiuwen Wang, Hui Luo, Baolan Li, Ben Zhang, Haowen Li, Ke Ma
Journal: Cancer Research (2022)

Abstract Introduction: Extensive-stage small cell lung cancer (ES-SCLC) is associated with limited treatment options and poor prognosis. Immunotherapy has recently showed robust clinical activity in ES-SCLC. In this double-blind, phase 3 trial, we evaluated adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, in combination with standard chemotherapy (chemo) as first-line treatment for ES-SCLC. Methods: Patients naïve to systemic treatment for ES-SCLC were randomized 1:1 to receive 4-6 cycles of adebrelimab (20 mg/kg, iv, d1, q3w) or placebo with carboplatin (AUC 5, d1, q3w) plus etoposide (100 mg/m2, d1, d2, d3, q3w), followed by maintenance therapy with adebrelimab or placebo. The primary endpoint was overall survival (OS). Results: 462 patients were randomized and treated (adebrelimab+chemo, n=230; placebo+chemo, n=232). As of Oct 08, 2021, with an median follow-up of 13.5 mo (all patients; 22.5 mo for patients alive), OS was significantly prolonged with adebrelimab+chemo vs placebo+chemo (median, 15.3 mo [95% CI 13.2-17.5] vs 12.8 mo [95% CI 11.3-13.7]; hazard ratio [HR], 0.72 [95% CI 0.58-0.90], 1-sided p=0.0017); OS rate was 62.9% vs 52.0% at 12 mo and 31.3% vs 17.2% at 24 mo. Progression-free survival (PFS) per independent review committee (IRC) was 5.8 mo (95% CI 5.6-6.9) with adebrelimab+chemo vs 5.6 mo (95% CI 5.5-5.7) with placebo+chemo (HR 0.67, 95% CI 0.54-0.83); PFS rate was 49.4% vs 37.3% at 6 mo and 19.7% vs 5.9% at 12 mo. Objective response rate (ORR) and duration of response (DoR) also favored the adebrelimab+chemo group (Table 1). Grade ≥3 treatment-related adverse events occurred in 85.7% vs 84.9% of patients with adebrelimab+chemo vs placebo+chemo, with the most common (frequency ≥5%) being hematological toxicities in both groups. Conclusions: The addition of adebrelimab to chemotherapy significantly improved OS with an acceptable safety profile, supporting this combination as a new first-line treatment option for ES-SCLC. Efficacy outcomes Adebrelimab+Chemo (n=230) Placebo+Chemo (n=232) Median OS (95% CI), mo 15.3 (13.2-17.5) 12.8 (11.3-13.7) HR (95% CI)*, 1-sided log-rank p 0.72 (0.58-0.90); p=0.0017 12-mo OS rate (95% CI), % 62.9 (56.3-68.8) 52.0 (45.4-58.2) 24-mo OS rate (95% CI), % 31.3 (24.9-37.9) 17.2 (12.1-23.0) Median PFS (95% CI), mo 5.8 (5.6-6.9) 5.6 (5.5-5.7) HR (95% CI)*, 1-sided log-rank p 0.67 (0.54-0.83); p &amp;lt;0.0001 6-mo PFS rate (95% CI), % 49.4 (42.4-56.0) 37.3 (30.7-43.9) 12-mo PFS rate (95% CI), % 19.7 (14.5-25.5) 5.9 (3.1-10.1) IRC-assessed ORR (95% CI), % 70.4 (64.1-76.3) 65.9 (59.5-72.0) Median DoR (95% CI), mo 5.6 (4.6-6.7) 4.6 (4.3-5.5) *Stratified Cox proportional-hazards model Citation Format: Ying Cheng, Jie Wang, Caicun Zhou, Wenxiu Yao, Qiming Wang, Xuhong Min, Gongyan Chen, Xingxiang Xu, Xingya Li, Fei Xu, Yong Fang, Runxiang Yang, Guohua Yu, Youling Gong, Jun Zhao, Yun Fan, Quan Liu, Lejie Cao, Yu Yao, Yunpeng Liu, Xiaoling Li, Jingxun Wu, Zhiyong He, Kaihua Lu, Liyan Jiang, Huiqing Yu, Chengping Hu, Wenhua Zhao, Jian Zhao, Gang Wu, Dingzhi Huang, Chengshui Chen, Cuimin Ding, Baihong Zhang, Xiuwen Wang, Hui Luo, Baolan Li, Ben Zhang, Haowen Li, Ke Ma. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage SCLC: A phase 3 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT038.